The cytochromes P-450 of the adrenal cortex, liver, lung and epitheleal tissues have been shown to mediate a wide range of oxidative metabolism including drug detoxification, steroid hydroxylation and carcinogenic activation. A detailed understanding of these vital processes is hampered by the transient and enigmatic properties of the oxidized intermediates of this heme-containing monooxygenase. Furthermore, the lack of any simple, molecular models of the "active oxygen species" prevents a conceptual apprach based on known chemistry. Our two-pronged approac to this problem has been to design substrates for cytochrome P-450 which will reveal the nature of oxygen activation and transfer and to develop synthetic metalloporphyrin models of the active site of cytochrome P-450 which will provide a molecular rationale for these processes. Deuterium labeling techniques and the monitoring of molecular rearrangements, which we have developed with model systems, have given evidence for carbon radical intermediates in the enzymic processes as well. The fate of these radicals may ultimately be linked to the hepatotoxicity of a large number of xenobiotic chemical contaminants.